ATPS-10DEXMEDETOMIDINE ALTERS MOLECULAR PROFILE AND CELLULAR PROPERTIES OF GLIOBLASTOMA

Abstract

Different cellular and molecular effects of the alpha-2-receptoragonist Dexmedetomidine have been reported and the drug is becoming of essence in glioblastoma (GBM) care for both, awake craniotomies and in postoperative intensive care. Glioblastoma stem cells (GSCs) are an established model for preclinical GBM research. However, the effects of Dexmedetomidine on GSCs expression profile is unknown. The purpose of this research was to establish the drugs impact on the expression profiles and cellular properties of GSCs. Two independent GSC lines were exposed to Dexmedetomidine. miRNA and mRNA expression profiling by microarrays was performed using total RNA. In silico analysis were performed with ingenuity pathway analyses (IPA) and gene ontology (GO) analysis. Changes in cellular properties such as self-renewal (limiting dilution assay), differentiation (neural lineage marker analysis), proliferation (BrdU labeling), and invasion (Boyden chamber assays) were investigated upon Dexmedetomidine treatment. Dexmedetomidine treatment altered the cellular and molecular profiles of GSCs. Ingenuity pathway analyses and gene ontology analysis of differentially expressed genes in Dexmedetomidine exposed cells revealed multiple cellular functions being potentially affected. Comprehensive in vitro experiments with GSCs including differentiation, proliferation, self-renewal and migration/invasion assays show that the alpha-2-receptor-agonist can potentially impact GBM pathogenesis by significantly altering cellular behavior of GSCs. With this in silico and in vitro approach we could show how Dexmedetomidine influences GSCs on cellular and molecular level. Respecting these results offers opportunities to enhance prognosis for patients being treated for GBM by adapting the usage of this alpha-2-receptor-agonist.